First Online: 12 May 2009Received: 29 January 2009Accepted: 30 April 2009

Abstract

The insulin variable number of tandem repeats INS VNTR has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 rs689 allele and birth length effect size 17.5 5.2–29.8 mm; P = 0.004; n = 361. Significant associations were also found between the maternally inherited African-specific SNP 28 rs5506 allele and post-natal weight gain effect size 0.19 0.05–0.32 z score points-year; P = 0.005; n = 728. These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.

AbbreviationsIGF2Insulin-like growth factor 2 gene

INSInsulin gene

LBWLow birth weight

qTDTQuantitative transmission disequilibrium test

SGASmall for gestational age

SNPSingle nucleotide polymorphism

VNTRVariable number of tandem repeats

C. J. Petry, P. Rayco-Solon, and A. J. C. Fulford contributed equally to this work and should be considered as equal first authors.

Electronic supplementary materialThe online version of this article doi:10.1007-s00439-009-0681-2 contains supplementary material, which is available to authorized users.